Pain can be modulated by explicit beliefs about treatments, prior experience and learning, interpersonal processes that support the patient-provider relationship, and contextual factors related to the treatment environment. In this project, we systematically investigate the neural and psychological mechanisms that mediate the effects of these factors on acute pain. We focus on expectations, attention, emotion, conditioning/associative learning, and social factors. Our experiments principally use functional magnetic resonance imaging (fMRI) and psychophysiological measurements, as well as behavioral assays and self-reports. We are examining the effects of different types of pain-related expectations on decisions about pain as well as responses in the brain and body, and we are comparing acute pain with other hedonic and perceptual processes (e.g. pleasant and unpleasant taste perception). This will allow us to distinguish processes that are unique to pain perception from those that are not specific to pain, such as processes involved in perception and decision-making across domains. This was the third year of the Section on Affective Neuroscience and Pain, and the lab continued to grow, adding one postdoctoral fellow and one additional postbaccalaureate research assistants. We also had three fellows complete their time in our lab successfully and move on to new positions: One postdoctoral fellow (DM) received a faculty position and two former post baccalaureate research assistants were accepted into PhD programs (Clinical Psychology and Behavioral and Cognitive Neuroscience). Our efforts this year were primarily focused on data collection on our human subjects protocol Neural and psychological mechanisms of pain perception. The protocol includes five sub-studies designed to a) isolate different aspects of pain modulation, b) compare acute pain modalities (e.g., thermal pain versus shock-induced pain), and c) compare and contrast pain with other hedonic and perceptual domains (e.g., taste). In all studies, we measure decisions about pain experience (self-report) as well as neural and physiological responses to noxious stimuli that cause pain. During analysis, we combine computational modeling with advanced neuroimaging analyses to isolate the neural and psychological mechanisms that mediate the effects of expectations, attention, and emotion on subjective pain. Our protocol requires all participants to go through an initial calibration session, following screening. Participants complete questionnaires, and then undergo a procedure that measures pain ratings in response to noxious heat stimuli and determines each participants pain threshold and tolerance. 183 individuals have completed this procedure to date (56 participants so far during Year 3 of the protocol, FY16-17). We analyzed the relationship between temperature, pain, and autonomic responses (skin conductance and pupil dilation), and found that autonomic responses to objective stimuli depend on whether a response is classified as painful or not. These data are currently under revision at the journal Pain (Mischkowski et al.). Furthermore, we found correlations between self-reported trait mindfulness and retrospective, but not online, pain reports. We are currently preparing these findings for manuscript submission (Mischkowski et al). In FY17 we completed our first fMRI sub-study, designed to examine the effects of classical conditioning and instructed knowledge on pain and reversal learning. Forty healthy volunteers successfully completed the fMRI task and we are currently analyzing fMRI data from these participants. Behavioral and physiological data were analyzed and presented by one of the postbaccalaureate fellows (EM) for NIHs Postbac Poster Day. Preliminary analyses (which combine fMRI data with data from our behavioral pilot study) indicate dissociations between cue-based expectancy effects on pain reports and skin conductance responses, and suggest that responses may be related to state anxiety. We are currently extending these analyses to identify neural correlates of these dissociations, and we have designed follow up in collaboration with Dr. Daniel Pine (NIMH) to test these effects in clinically anxious individuals. We also began a second fMRI sub-study designed to test whether cue-based expectancies and treatment-based expectancies (i.e. placebo responses) modulate pain through dissociable pathways. This study crosses conditioned cues with a placebo analgesia manipulation. During FY16 and the beginning of FY17, seventeen individuals completed a behavioral pilot task that allowed us to compute power analyses prior to beginning the fMRI version of the experiment. FMRI scanning began in the spring of 2017, and we will continue scanning until 40 participants complete the task. We expect to complete the fMRI study in the first half of FY18. We worked with the Section on Instrumentation to build a gustometer (taste-delivery device) that can deliver juices in the fMRI scanner and began a behavioral pilot sub-study in the NCCIH mock scanner that administers heat along with pleasant and unpleasant liquid tastants. Our goal is to examine the relationship between pain and taste and how expectations modulate perceptions across domains. Participants undergo a calibration procedure to identify pleasant and unpleasant tastants which parallels our pain calibration procedure and allows us to individually calibrate tastants for each individual. Participants then complete conditioning followed by sensory testing with each modality, which allows us to measure the effects of cue-based expectations on affective experience in each modality. 16 participants have completed behavioral testing. After 2 more participants complete testing, we will conduct power analyses to determine the appropriate sample size for fMRI testing. We expect to begin fMRI testing in FY18 when two new postdocs join the lab. The overall goal of this project is to isolate domain-specific as well as domain-general mechanisms that underlie expectancy, affective learning, and perception. We have also nearly completed behavioral testing on a sub-study that measures the relationship between attention, expectations, and learning. 16 participants have completed the behavioral sub-study. When 18 have completed, we will conduct power analyses to determine the required sample size for an fMRI version of this paradigm. Finally, we received IRB for a new protocol, 17-AT-0155, Sociocultural & Biobehavioral Influences on Pain Expression and Assessment. This protocol measures pain-related facial responses in a diverse population to measure whether nonverbal responses to pain vary as a function of biological and sociocultural factors. We then also measure whether individuals (both healthy volunteers and medical providers) pay attention to different features of pain or assess pain differently in in-group relative to out-group individuals, and whether we can develop interventions to reduce any biases in attention or pain assessment. We expect data collection to begin on our first sub-study in this protocol in early FY18.